Project Summary/Abstract Objective(s): The most frequent co-occurring Axis I disorder with substance use disorders is depression, and Posttraumatic Stress disorder (PTSD) is also common in substance treatment samples. Not surprisingly, the combination of these three disorders is also common, particularly within the VA. We have demonstrated the efficacy of our newly developed Integrated Cognitive Behavioral Therapy (ICBT) for substance dependent veterans with depression, providing two phases of treatment: Phase I with twice weekly sessions for 12 weeks, followed by Phase II of once weekly sessions for an additional 12 weeks. Forty percent of our sample also met criteria for PTSD and 80% had experienced a trauma, with symptoms that did not reach diagnostic levels. The goal of this study is to evaluate the clinical utility of providing an evidenced based trauma intervention (Cognitive Processing Therapy: CPT) following Phase I of our ICBT intervention for veterans with depression, substance disorder, and trauma exposure (with and without PTSD). We propose to modify CPT to integrate substance relapse prevention strategies, similar to our ICBT intervention. Thus, we will provide all participants with the initial 12-week group ICBT intervention (Phase I), anticipating a reduction in substance use and depression symptoms as shown in our prior study. This will prepare veterans to successfully participate in sensitive trauma focused therapy. Following completion of Phase I, we will randomize veterans to receive either ICBT (as was done in our prior study for depression and SUD) or the newly modified CPT. Findings from our prior study documented that veterans with PTSD (and depression and SUD) had worse outcomes for both depression and substance use than veterans without PTSD, particularly in the year after completing the intervention. The goal of the current study is to provide a trauma specific intervention as follow-up with the aim of improving outcomes and preventing the deterioration observed in our prior study. Research Design: This 4-year study is a randomized clinical trial with two treatment groups and repeated quarterly research assessments for 18 months. Assessment interviews will be completed at intake, end of Phase I of treatment (12 weeks), end of Phase II of treatment (24 weeks), and every 3 months thereafter for one year following treatment completion. We will assess depression symptoms (Hamilton Depression Rating Scale and Beck Depression Inventory), PTSD symptoms (PTSD Checklist), and substance use (percentage days abstinent assessed with Timeline Followback) as the primary outcomes. Veterans will be recruited from the Substance Abuse Mental Illness (SAMI) Clinic at the VA San Diego. As in our prior ICBT study, all participants will meet with the SAMI program psychiatrist approximately monthly for medication evaluation using standard VA pharmacotherapy protocol. Veterans with depression, substance dependence, and a history of trauma will be included. We propose to recruit 180 veterans, with anticipated attrition of approximately 30% (20% during 24 week treatment, 10% during year follow-up) based on our prior ICBT study, providing a final sample of 130, with adequate power to detect based on our prior findings. PUBLIC HEALTH RELEVANCE: Project Narrative Substance use disorders (SUD) are a high priority group within the VA system. VA research shows that more than a quarter of inpatient services and half of psychiatry services are provided to patients with SUD history. The severe mental illnesses that are the focus of this proposal (depression, PTSD) are also prevalent and a high priority within the VA. The co-occurrence of two of these disorders increases risk of poor treatment outcomes, risk of suicide, and health service costs. The co-occurrence of all three worsens outcomes further, highlighting the critical need for research to inform optimal treatment decisions for these high-risk veterans. Development of interventions for co-occurring SUD, depression, and PTSD will improve the care provided to veterans.